Abstract
Abstract Introduction Eosinophilic esophagitis (EoE) is food-triggered immune esophageal disease characterized by dysphagia and food impaction. The pathophysiology of EoE is poorly understood. Prior eosinophilic esophagitis studies showed abundant IgG4 with IgG4+ plasma cells in esophageal subepithelial tissue. Methods Seven esophagectomies and one deep biopsy from patients with active EoE were compared. Seven uninvolved esophageal areas from surgical resections for tumor and autopsy were used as controls. Histology, immunostains, RNA in situ hybridization, and RNA-seq findings were compared with EoE epithelial biopsy RNA-seq. Results The superficial lamina propria (LP) of EoE patients has dense fibrosis, tertiary lymphoid tissue with abundant B cells, IgG4 plasma cells, and Foxp3+ regulatory T cells. RNA-seq confirms this, with abundant B cell related transcripts, IGHG4, organized lymphoid tissue marker CCL21, and regulatory T cell markers. IL-10 in situ hybridization is present in mononuclear cells, in and near lymphoid aggregate germinal centers. Edema and degranulating mast cells are absent. By RNAseq, the LP of both eosinophilic esophagitis patients and controls have abundant thrombospondin-1, which could activate TGFβ. Nuclear immunostaining for phosphoSMAD2 and phosphoSMAD3 (suggesting active TGFβ), is present the epithelium and the superficial lamina propria. Conclusion The EoE LP immune response has abundant IgG4 plasma cells, regulatory T cells, and a predominantly immunoregulatory transcriptome. Some LP immunoregulatory features are present even in controls. Further work is needed to determine whether the immunoregulatory infiltrate contributes to the dysphagia-inducing subepithelial fibrosis.
Published Version
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